Project Summary/Abstract: We are requesting funds for a new JEOL JEM-2100PLUS transmission electron microscope (TEM) to replace an obsolete (>25 years old) CM-12 FEI Thermo Fisher for which we can no longer obtain a service contract. (Please see the letter from Kevin Hogarty in the Letters section.) We have a very busy EM Core Research Laboratory for which access to a high-resolution microscope is essential. In the 4+ decades of existence of the EM Core Laboratory, we have served over 300 different laboratories, most of which brought multiple projects for ultrastructural analysis. At any one point in time, we usually juggle 10-15 different projects, many of which are fully handled by the EM staff from beginning to end. The 22 major and minor users are all current (this year) and all, except one young minor user, have NIH grants. Before starting any project, we meet with researchers and counsel them up front what the prospects for success are, how to design experiments, and how to submit specimens. Students and faculty may come to view specimens in the EM themselves or may receive complete data produced by the staff; they are also coached on interpretation of the micrographs. In some cases, we teach students to process their own samples and operate the EM. Examples of projects include negative stains of viruses and virus-like particles, subviral particles (e.g., glycoprotein spikes), and subcellular organelles (e.g., mitochondria); unstained preparation of nanoparticles; and thin sections of tissues from many organisms and tissue cultures. The TEM also supports work on the serial block face scanning electron microscope (SBFSEM) in that it is used to confirm proper specimen preparation and to select regions of interest before loading the blocks into the 3D microscope. By performing this quality assurance step by TEM, we save valuable time on the SBFSEM. No other EM on campus nor collective time on all the EMs is capable of handling all our EM Core clients. (Please see letters from Drs. Arshavsky, Boswell Edwards, and Walters.) We explored the possibility of a newer used TEM, but they were ~$100-200K and were almost as old as ours; thus, with this option, we would be back in the sample place in a few years. Also, we looked into obtaining a service contract from an outside company, but they would have to purchase parts from the current company that is reluctant to sell parts. One outside service company assured us that they could service our EM and do it for less money, but after conferring with his leadership, told us that they could not service our brand because that company would not sell them parts. Obtaining the new instrument will permit the Core EM Facility to continue providing excellent ultrastructural data to NIH investigators. Without it, when the old microscope goes down in the near future, we will not be able to keep the laboratory open.